1,2-Dialkyl-3(or 3,5)-N-heterocyclic pyrazolium salts of derivatives thereof as fungicidal agents

ABSTRACT

There is provided a method for controlling fungi with a fungicidally effective amount of a 1,2-dialkyl-3(or 3,5)-N-heterocyclic pyrazolium salt. There is also provided a method for protecting living plants from attack by fungi through the application to the foliage of said plants of a fungicidally effective amount of such pyrazolium salt compounds.

The present invention relates to a method for controlling fungi withpyrazolium compounds which have a nitrogen containing heterocyclic groupeither in the 3 position, or in the 5 position or in the 3 and 5positions of the pyrazolium ring and are represented by a formula:##SPC1##

Wherein R₃ is a member selected from the group consisting of hydrogen,methyl, hydroxy and phenyl; R₄ represents a member selected from thegroup consisting of hydrogen or halogen; R₅ represents a member selectedfrom the group consisting of phenyl, cyclohexyl and ##EQU1## Xrepresents an anion with a charge of 1 or 2 and preferably 1; nrepresents an integer selected from 4, 5 and 6; m represents an integerselected from 1 and 2; and HB represents an inorganic or organic acid.

As employed in the present application the term "halogen" is intended tomean fluorine, chlorine, bromine and iodine; however, bromine ispreferred.

Illustrative of the anions, represented by X, which are suitable for usein the present invention are, for example, halides such as chloride,bromide or iodide; acetate; sulfate, hydroxide; hydrogen sulfate; methylsulfate; benzene sulfonate; alkoxy (C₁ -C₄) benzene sulfonate: alkyl (C₁-C₃) benzene sulfonate, such as, p-toluene sulfonate; nitrate;phosphate; tetrafluoroborate, (C₆ H₅)₄ B; iodate; alkane sulfonate (C₁-C₄); perchlorate; Br₃ ⁻ and I₃ ⁻.

With regard to the pyrazolium salts of formula (I), it is to beunderstood that certain multivalent anions such as sulfate, phosphate,and the like may have associated with them a cation in addition to thepyrazolium, as for example a proton or an alkali metal or alkaline earthmetal. For simplicity, such anions are characterized as being unionized,although they probably are further ionized in fact. Typicalrepresentations are: NaSO₄ ⁻, KPO₄ ⁼, MgPO₄ ⁻, HSO₄ ⁻, and NaHPO₄ ⁻.

Illustrative of the acid residue, identified in formula (II) above as .HB, which is suitable for use in the present invention are (a) inorganicacids, such as HCl, HI, HBr, HClO₄, H₂ SO₄, HNO₃ and H₃ PO₄ and (b)organic acids, such as CH₃ SO₃ H, ##SPC2##

ClCH₂ COOH, and other organic acids of sufficient acid strength to formstable salts with ##EQU2## group.

Preferred compounds useful for the practice of the method of thisinvention are represented by above-identified formulas (I) and (II),respectively, wherein R₃ is hydrogen or methyl; R₄ is hydrogen, R₅ isphenyl, or cyclohexyl; n is 5; m is 1 or 2; and X is an anion with acharge of 1 or 2.

Exemplary of the effective compounds useful in the present inventionare:

1,2-Dimethyl-3-phenyl-5-piperidinopyrazolium iodide, hydroiodide,

1,2-Dimethyl-3-phenyl-5-piperidinopyrazolium perchlorate, perchloricacid salt,

1,2-Dimethyl-3-phenyl-5-(1-pyrrolidinyl)pyrazolium methyl sulfate,

3-(Hexahydro-1H-azepin-1-yl)-1,2-dimethyl-5-phenylpyrazolium iodide,

1,2-Dimethyl-3-(4-methylpiperidino)-5-phenylpyrazolium iodide,

1,2-Dimethyl-3-(2-methylpiperidino)-5-phenylpyrazolium iodide,1,2-Dimethyl-3-(3-methylpiperidino)-5-phenylpyrazolium iodide,

4-Bromo-1,2-dimethyl-3,5-dipiperidinopyrazolium bromide, hydrobromide,

4-Bromo-1,2-dimethyl-3,5-dipiperidinopyrazolium perchlorate, perchloricacid salt,

1,2-Dimethyl-3,5-dipiperidinopyrazolium bromide, nitric acid salt,

1,2-Dimethyl-3,5-dipiperidinopyrazolium perchlorate,

1,2-Dimethyl-3-(3-methylpiperidino)-5-phenylpyrazolium perchlorate,

1,2-Dimethyl-3-(3-methylpiperidino)-5-phenylpyrazolium bromide,

1,2-Dimethyl-3-(3-methylpiperidino)-5-phenylpyrazolium methyl sulfate,

1,2-Dimethyl-3-(3-piperidino)-5-phenylpyrazolium chloride,

1,2-Dimethyl-3-(2-methylpiperidino)-5-phenylpyrazolium methyl sulfate,

3-Cyclohexyl-1,2-dimethyl-5-(3-methylpiperidino)pyrazolium methylsulfate (and chloride),

1,2-Dimethyl-3-(2-methylpiperidino)-5-phenylpyrazolium perchlorate,

1,2-Dimethyl-3-(2-methylpiperidino)-5-phenylpyrazolium chloride,hydrochloride,

3-Cyclohexyl-1,2-dimethyl-5-(3-methylpiperidino)pyrazolium iodide,

3-Cyclohexyl-1,2-dimethyl-5-piperidinopyrazolium iodide,

1,2-Dimethyl-3-(3-hydroxypiperidino)-5-phenylpyrazolium iodide,

In accordance with the invention, compounds of formula (I) defined abovecan be synthesized from an intermediate (IV), defined below, by reactionof the intermediate 3-halopyrazolium compounds (IV) with a saturatedazaheterocycle or a saturated N-containing heterocycle (III) hereinbelowdefined within a temperature range of from about 20°C. to about 100°C.In this reaction it is necessary to include either two moles of theazaheterocycle, one as a base acceptor, or to use one mole ofazaheterocycle and one mole of an organic or inorganic base acceptor. Inpractice tertiary amines, such as trimethylamine, triethylamine,pyridine or quinoline as well as inorganic bases, such as sodiumbicarbonate, sodium carbonate and the like can be employed.

The reaction is graphically illustrated as "Method A" as follows:##SPC3##

where R₃, R₄, R₅, m, n and X are each as defined above. This reactioninvolves displacement of a halogen by a azaheterocycle group.Additionally a variety of inert solvents such as methanol, ethanol,propanol, dimethylformamide (DMF), acetone, acetonitrile or the like canbe utilized during reaction.

A limitation to this procedure is reaction temperature and time. Heatingthe (IV) compound with an excess of azaheterocycle, especially attemperatures above 100°C. over an extended time, causes increasingdealkylation of the pyrazolium compound (I) to the pyrazole. Thus, toprevent dealkylation, the preferred reaction temperature is 80°C., orless, and preferably 40°C. to 80°C.

The counter ion X employed in the Method A may be any of those listed,although methyl sulfate, iodide, bromide, chloride, perchlorate, andtetrafluoroborate are generally preferred. The product identified byformula (I) may be prepared with a particular anion X either by reactingcompound IV containing the required anion X or by alternative proceduresoutlined below. For example, the anion of (I) may be replaced either byexchange chromatography (Method A) on an appropriately modified Dowex1-X8 base anion exchanged or in some cases by the addition of aconcentrated solution of an acid salt (Method A salt) e.g. utilizingsodium iodide, sodium tetrafluoroborate, or sodium perchlorate [or 10%aqueous perchloric acid (Method A acid)], thereby causing the waterinsoluble salt to precipitate. When an acid is used as, for instance,perchloric acid, not only does ion exchange occur, but there also mayoccur the formation of a perchlorate salt of the azaheterocyclic group.

Purification of a formula (I) compound above can be effected bydissolving said compound in water, excepting the water insoluble salts,such as perchlorate or iodide, and washing the aqueous layer with ether,discarding the ether layer, then extracting the same with chloroform ormethylene chloride. Product (I) may then be precipitated from thechlorinated hydrocarbon by the addition of diethyl ether.

The preparation of 3-halopyrazolium compound (IV) employed in Method Acan be accomplished by the stepwise reactions involving: (1) a benzoylacetic acid ester or a cycloalkanoyl acetic acid ester (V) defined moreparticularly hereinbelow with methyl hydrazine to yield a3-pyrazolinones (VI), (2) halogenation of said pyrazolinone (VI) withphosphorus oxyhalide to yield the corresponding 3-halopyrazole (VII),and (3) methylation of said 3-halopyrazole (VII) to yield a3-halopyrazolium compound (IV). Conversion of the formula (IV)3-halopyrazolum salt to the formula (I) pyrazolium salt containing, the3-nitrogen heterocyclic group is readily achieved by reaction of thehalopyrazolium salt with an azaheterocycle in the presence of base, asdescribed above.

The four reaction steps are graphically illustrated below withphosphorus oxychloride used to represent the oxyhalide employed as thehalogenation reagent of the pyrazolinone (VI). ##SPC4##

where R₃, R₄, R₅, m and n are each as defined above.

The methylation reaction in Step 3 above is preferably conducted in thepresence of a solvent, such as xylene, toluene, benzene,1,2-dichloroethane or the like. Alternatively, it may be conducted tothe exclusion of a solvent using solely the halopyrazole (VII) reactantand the alkylating agent.

Illustrative methylation reagents include, methyl sulfate, methylhalides, methyl hydrogen sulfate, methyl toluene sulfonate and the like.

In general, the halopyrazole and methylating reagent combine on anequimolar basis. However, it is a good practice to employ an excess ofthe methylating agent. Optimum reaction conditions for effecting themethylations will vary depending on the reactants employed. Reaction iseffected by combining the methylating agent and an halopyrazole usuallyin the presence of a solvent. The reaction mixture is heated until thereaction occurs. Where the methylating reagents employed are volatile,such as methyl chloride, the reaction is preferably conducted in asealed vessel under pressure, to avoid loss of the reactants. Thequaternization of the formula (IV) 3-halopyrazolium compound isaccomplished by utilizing a methylating agent, such as dimethylsulfate,methyl chloride, methyl iodide or other such agent, alone or admixedwith a solvent.

The preparation of formula (IV) 3-halopyrazolium compounds where R₄ ishalogen, can be accomplished by direct halogenation of the1-methyl-3-halopyrazole (VII) in acetic acid.

Compounds containing 3,5-disubstituted azaheterocyclic substituents (IX)can be prepared by a process, hereinafter referred to as Method B. Thismethod involves the reaction of a 3,5-dihalopyrazolium compound with anazaheterocycle; both 3 and 5-dihalogens react rapidly at ambienttemperatures up to 80°C. However, under these conditions, thesubstituent in the 4-position, even a 4-halogen, is unreactive to anazaheterocycle. The reaction is preferably conducted in the presence ofa base and an aprotic solvent such as xylene, toluene, benzene or thelike. This reaction "Method B" is graphically illustrated as follows:##SPC5##

where R₃, R₄, m and n are each as defined above.

In practice it has been found that formula (X)3,5-diazaheterocyclylaminopyrazolium compounds where R₄ is hydrogen, canbe most advantageously prepared from formula (IX)3,5-diazeheterocyclylamino-4-halopyrazolium compounds by adehydrohalogenation process, hereinafter referred to as "Method C". Theprocess involves the reaction of a3,5-diazaheterocyclylamino-4-halopyrazolium salt (XI) with hydrogen, inthe presence of a strong base such as an alkali metal alkoxide (e.g.sodium methoxide, sodium ethoxide or potassium t-butoxide) and acatalyst such as palladium or platinum on carbon. The reaction ispreferably conducted at a temperature between about 20°C. and 40°C. andmay be illustrated as follows: ##SPC6##

As noted above, the hereinabove recited compounds are effective for thecontrol of fungi which infect many living plants. They are particularlyeffective for controlling powdery mildew, especially on grains such asbarley, corn, sorghum and wheat, on vines such as cucumbers, grapes andpumpkin and on fruit and nut trees such as apples, pears and pecans.However, they are also effective for controlling fungi which are thecausative agents for other diseases such as rice blast, and apple scab.

In utilizing the above-identified pyrazolium salts for protecting plantsfrom pathogenic fungi, it has been found most advantageous to apply thecompounds herein foliage of the plant in the form of a liquid,preferably aqueous, spray. Solutions or suspensions containing fromabout 100 to 5600 ppm, and preferably 100 to 1000 ppm of the pyrazoliumsalt, are generally highly effective for this use.

For application as liquid sprays, said compounds are generally preparedas emulsifiable concentrates, wettable powders, or water miscibleconcentrates which are diluted with water or other suitable polarsolvents, and then applied as a dilute spray. Generally such sprays areapplied at the volume rate of about 938 liters to 1877 liters/hectare(l/ha) or about 100 or 200 gal per acre. It is, of course, obvious thatsmaller or larger volumes of liquid spray may be employed, eg., 400 to4000 l/ha may be used depending on a variety of factors including thetype of crop, the plant spacing and the amount of foliage per plantbeing treated.

Wettable powder formulations can be prepared by grinding together about25% to 95% by weight of the pyrazolium salt and about 75% to 5% byweight of a solid diluent such as attapulgite, kaolin, bentonite,diatomaceous earth, silica, talc, fullers earth or the like. To thismixture is added about 1% to 5% by weight of a dispersing agent, such asthe calcium salt of a polymerized alkyl aryl sulfonic acid, sodiumlignosulfonate, or sodium salt of condensed naphthalene sulfonic acid,and about 1% to 5% by weight of a surfactant, such as polyoxyethylatedvegetable oil, alkyl phenoxy polyoxyethylene ethanol, sodium alkylnaphthalene sulfonate, is also blended with the formulation.

The water-miscible concentrates are prepared by dissolving from 15% to70% by weight of the compound in 85% to 30% by weight of awater-miscible solvent, such as water itself or another polarwater-miscible solvent, such as 2-methoxy ethanol, methanol, propyleneglycol, diethylene glycol, diethylene glycol monoethyl ether, formamide,and methylformamide. Application of the material is made by adding apredetermined quantity of the water-miscible concentrate to a spray tankand applying as such or in combination with additional suitable diluent,such as a further quantity of water or one of the above polar solventsmentioned above.

The performance of the product in the above formulations, which areapplied as liquid sprays, is improved by adding a surfactant or blend ofsurfactants thereto. Conventional nonionic surfactants are preferred andthe surfactants are preferably added to the formulation or the spraytank at the rate of 0.1% to 5% by volume to provide good wetting of thespray solution on plant foliage.

Suitable nonionic surfactants include alkyl polyoxyethylene ethers,polyoxyethylene (20) sorbitan monolaurate, polyoxyethylene (20) sorbitanmonooleate, alkylarylpolyglcol ethers, alkyl phenol ethoxylates,trimethyl nonyl polyethylene glycol ethers, alkyl phenol ethylene oxidecondensates, octyl phenoxy polyethoxy ethanols, nonylphenyl polyethyleneglycol ethers, condensates of polyoxy ethylenes, polyoxy propylenes,aliphatic polyethers, aliphatic polyesters, alkylarly poloxyethyleneglycols, and the like. Especially preferred nonionic surfactants havinga hydrophilic-lipophilic balance (HLB) of from 11 to 16. Thisconventional surfactant classification test is described, for example,at page 232 et seq of Emulsion Theory and Practice by Paul Becker,Rheinholt Publishing Corporation, second edition (1965); also availableas No. 162 in the American Chemical Society's Monograph Series.

Generally, the plants which are to protected against attack from fungalorganisms are sprayed to run off with solutions or suspensions of theabove-identified compounds. In practice it has been found that solutionsor suspensions containing from about 100 to 5600 ppm of the compoundsherein and preferably 100 to 1000 ppm of such compounds afforded thedesired protection.

In order to facilitate a further understanding of the invention, thefollowing examples are presented primarily for purposes of illustratingcertain more specific details thereof. The invention is not to be deemedlimited thereby except as defined in the claims. Unless otherwise noted,the parts are by weight.

EXAMPLE 1

To determine the effectiveness of the 1,2-dialkyl-3(or 3,5)-mono(ordi)heterocyclic pyrazolium salts as fungicidal agents, a variety ofpathogenic fungi, host plants and acid salts are used in the followingtests. Pathogens, host plants, the method of testing, the rating systemused, and the data obtained are set forth below.

Pathogens:

Piricularia oryzae Cavara, the rice blast pathogen.

Venturia inaequalis (Cke.) Wint. which causes apple scab.

Erysiphe cichoracearum DC, the cause of powdery mildew on cucurbits.

Podosphaera leucotricha (E. & E.) Salm., the cause of powdery mildew ofapples and pears.

Erysiphe graminis f. sp. tritici the cause of powdery mildew on wheat.

Erysiphe graminis f. sp. hordei the cause of powdery mildew on barley.

Host Plants:

Rice (Oryza sativa) Cv. Nato)

Cucumber (Cucumis sativus) (Cv. Marketer)

Apple (Malus sylvestris) (Seedling)

Wheat (Triticum aestivum Cv. Bonanza)

Barley (Hordeum vulgare Cv. Larker)

Plants are individually grown in 5.08 cm peat squares and assembled in7.62 cm. × 25.4 cm. pressed fibre containers the week prior to spraying.With exception of rice, barley, and wheat, a single specimen of eachspecies is used. A separate container is used for those plants in themildew evaluation. The complete test system is shown below.

    ______________________________________                                        Series 1        Series 2                                                      ______________________________________                                        Rice:   Rice Blast  Apple:     Powdery Mildew                                 Apple:  Apple Scab  Cucumber:  Powdery Mildew                                                     Wheat:     Powdery Mildew                                                     Barley:    Powdery Mildew                                 ______________________________________                                    

Spray solutions are prepared at a final concentration of 100 ppm or 500ppm in 50 ml of 50% aqueous acetone. Acetone is added to solubilize thetest compound and solutions made to final volume with deionized water.

Two containers, one each from Series 1 and 2 (see above), are sprayedsimultaneously on a turntable with 50 ml of the test solution. Spray isprovided by two fixed spraying nozzles mounted to deliver vertical andhorizontal solid cone spray patterns. Immediately thereafter, all plantsare returned to the greenhouse to permit the deposit to dry. Plants ofSeries 1 and 2 are separately inoculated. Plants in Series 1 areinoculated with conidial suspensions of the respective pathogens using apaint sprayer operated under 4-6 psig and, immediately, are transferredto a controlled temperature/humidity cabinet (ambient temperature,RH˜95%). Plants in Series 2 are dusted with respective powdery mildewconidia and then removed to the controlled environment plant cultureroom (10 hours light, ˜22°C., RH 45%) to await disease development.Plants in Series 1 are held 4 days in the cabinet, then transferred tothe greenhouse to await disease expression.

Performance Rating

All plants are rated for disease severity on a scale of 1 to 7 (clean tokill), as described below:

    Rating            Description                                                 ______________________________________                                               1          Clean                                                              2          Trace disease                                                      3          Slight disease                                                     4          Moderate disease                                                   5          Heavy disease                                                      6          Severe disease                                                     7          Kill                                                        ______________________________________                                    

In the tables hereinbelow presented, the numerical rating is used forclarity. Data obtained are reported in Tables I and II below. Theratings reported represent data obtained from one or more individualtests. Where more than one test has been conducted, the ratings areaveraged and reported as a single value rating. For each table, there isalso provided a rating value for the checks employed and a rating rangefor acceptable disease control. It is, of course, obvious that the lowerthe value, the more effective the disease control.

                  Table I                                                         ______________________________________                                        Disease Severity of Plants Sprayed to Run-off                                 with Indicated Rates (ppm)                                                    Compound             Rice Blast                                                                              Apple Scab                                                        500  100    500    100                                     ______________________________________                                        Acceptable Level of Control                                                                        1-4       1-4                                            Untreated Controls Average Rating                                                                  5.1       5.4                                            ______________________________________                                        1,2-Dimethyl-3-phenyl-5-piperidino-                                                                              3.0                                        pyrazolium iodide                                                             1,2-Dimethyl-3-phenyl-5-(1-pyrrolidinyl)-                                                                        4.0                                        pyrazolium methyl sulfate                                                     1,2-Dimethyl-3-(4-methylpiperidino)-5-                                                                           4.0                                        phenylpyrazolium iodide                                                       1,2-Dimethyl-3-(3-methylpiperidino)-5-                                                                           4.0                                        phenylpyrazolium bromide                                                      1,2-Dimethyl-3-(3-methylpiperidino)-5-                                                                           3.5                                        phenylpyrazolium perchlorate                                                  1,2-Dimethyl-3-(3-methylpiperidino)-5-                                                                           4.0                                        phenylpyrazolium methyl sulfate                                               1,2-Dimethyl-3-(3-methylpiperidino)-5-                                                             3.0           4.0                                        phenylpyrazolium chloride                                                     1,2-Dimethyl-3-(2-methylpiperidino)-5-                                                             4.0                                                      phenylpyrazolium perchlorate                                                  3-Cyclohexyl-1,2-dimethyl-5-(3-methyl-                                        piperidino)pyrazolium methyl sulfate                                          (and chloride)                                                                3-Cyclohexyl-1,2-dimethyl-5-(3-methyl-                                                                           2.0  3.0                                   piperidino)pyrazolium iodide                                                  3-Cyclohexyl-1,2-dimethyl-5-piperidino-                                                            4.0           2.0  3.0                                   pyrazolium iodide                                                             4-Bromo-1,2-dimethyl-5-(3-methyl-       3.0                                   piperidino)-3-phenylpyrazolium iodide                                         4-Bromo-1,2-dimethyl-5-(4-methyl-  2.0  3.0                                   piperidino)-3-phenylpyrazolium iodide                                         4-Bromo-1,2-dimethyl-3-phenyl-5-                                                                   4.0           4.0                                        piperidino-pyrazolium iodide                                                  4-Bromo-1,2-dimethyl-3-(2-methylpiperi-                                                                          1.0                                        dino)-5-phenylpyrazolium perchlorate                                          3-(3-Hydroxypiperidino)-1,2-dimethyl-5-                                                                          1.0                                        phenylpyrazolium perchlorate                                                  ______________________________________                                    

                                      Table II                                    __________________________________________________________________________    Disease Severity of Plants Sprayed to Run-off with Indicated Rates (ppm)                        Cucumber                                                                            Wheat Apple Barley                                    Compound          Powdery                                                                             Powdery                                                                             Powdery                                                                             Powdery                                                     500                                                                              100                                                                              500                                                                              100                                                                              500                                                                              100                                                                              500                                                                              100                                    __________________________________________________________________________    Acceptable Level of Control                                                                     1-4   1-3   1-3   1-4                                       Untreated Controls Average Rating                                                               6.0   5.9   5.6   5.4                                       __________________________________________________________________________    1,2-Dimethyl-3-phenyl-5-piperidino-                                                             4.0   2.3                                                                              3.0                                                                              3.3                                                                              3.5                                                                              4.0                                                                              4.0                                    pyrazolium iodide                                                             3-(Hexahydro-1H-azepin-1-yl)-1,2-                                                               4.0   3.0   4.0                                             dimethyl-5-phenylpyrazolium iodide                                            1,2-Dimethyl-3-(4-methylpiperidino)-                                                            1.0   2.0   3.0                                             5-phenylpyrazolium iodide                                                     1,2-Dimethyl-3-(2-methylpiperidino)-                                                                  2.8         3.3                                                                              4.3                                    5-phenylpyrazolium iodide                                                     1,2-Dimethyl-3-(3-methylpiperidino)-                                                                  1.0                                                                              4.0                                                                              3.0   1.0                                                                              3.0                                    5-phenylpyrazolium iodide                                                     1,2-Dimethyl-3-(3-methylpiperidino)-                                                            2.7   2.0                                                                              2.5                                                                              3.3                                                                              2.5                                                                              2.5                                                                              4.0                                    5-phenylpyrazolium bromide                                                    1,2-Dimethyl-3-(3-methylpiperidino)-                                                            4.3   2.3   4.3   3.5                                       5-phenylpyrazolium perchlorate                                                1,2-Dimethyl-3-(3-methylpiperidino)-                                                            3.0         4.0                                             5-phenylpyrazolium methyl sulfate                                             1,2-Dimethyl-3-(3-methylpiperidino)-                                                                  1.0   1.0                                             5-phenylpyrazolium chloride                                                   1,2-Dimethyl-3-(2-methylpiperidino)-                                                                  3.3   4.0   3.5                                       5-phenylpyrazolium chloride hydro-                                            chloride                                                                      1,2-Dimethyl-3-(2-methylpiperidino)-                                                            4.0   4.0                                                   5-phenylpyrazolium perchlorate                                                1.2-Dimethyl-3-(2-methylpiperidino)-                                                            4.0                                                         5-phenylpyrazolium methyl sulfate                                             3-Cyclohexyl-1,2-dimethyl-5-(3-                                                                 4.0   1.0                                                                              3.0   3.0                                                                              2.0                                                                              4.0                                    methylpiperidino)pyrazolium methyl                                            sulfate and chloride                                                          3-Cyclohexyl-1,2-dimethyl-5-(3-                                                                 1.0                                                                              4.0                                                                              2.0                                                                              4.0                                                                              4.0   3.0                                                                              4.0                                    methylpiperidino)pyrazolium iodide                                            3-Cyclohexyl-1,2-dimetyl-5-piper-                                                               1.0   2.0                                                                              4.0                                                idinopyrazolium iodide                                                        4-Bromo-1,2-dimethyl-5-(3-methyl-                                                                     2.0                                                                              3.0      2.0                                                                              3.0                                    piperidino)-3-phenylpyrazolium                                                iodide                                                                        4-Bromo-1,2-dimethyl-3-phenyl-5-                                                                      3.0                                                                              4.0                                                                              4.0   4.0                                       piperidinopyrazolium iodide                                                   __________________________________________________________________________

EXAMPLE 2

The fungicidal activity of the compounds of the present invention isdemonstrated in the following tests.

Wheat plants are individually grown in 5.08 cm peat squares andassembled in containers the week prior to spraying.

Spray solutions are prepared at a final concentration of 500 ppm in50%/50% water/acetone mixtures. The plants are placed on a turntable andsprayed with 50 ml of test solution. Immediately thereafter they areplaced on greenhouse benches and permitted to dry. After drying, saidtreated plants are dusted with powdery mildew spores and the dustedplants are then placed in a constant temperature room (22°C 10 hourslight and 45% RH) for from 7 days to 9 days to await disease expression.At the end of the holding period, all plants are examined and ratedaccording to the performance rating system provided below.

Performance Rating

All plants were rated for disease severity on a scale of 1 - 7 (clean -kill), as described in Example I above.

Data obtained are reported in Table III below.

                  Table III                                                       ______________________________________                                        Control of Powdery Mildew on Wheat                                                                    Rate   Disease                                        Compound                ppm    Severity                                       ______________________________________                                        1,2-Dimethyl-3-(3-methylpiperidino)-                                                                  500    1-Clean                                        5-phenylpyrazolium chloride                                                   1,2-Dimethyl-3-(3-methylpiperidino)-                                                                  500    1-Clean                                        5-phenylpyrazollium perchlorate                                               1,2-Dimethyl-3-(3-methylpiperidino)-                                                                  500    1-Clean                                        5-phenylpyrazolium iodide                                                     1,2-Dimethyl-3-(4-methylpiperidino)-                                                                  500    2-Trace                                        5-phenylpyrazolium iodide                                                     1,2-Dimethyl-3-(2-methylpiperidino)-                                                                  500    2-Trace                                        5-phenylpyrazolium iodide                                                     3-(Hexahydro-1H-azepin-1-yl)-1,2-                                                                     500    3-Slight                                       dimethyl-5-phenylpyrazolium iodide                                            1,2-Dimethyl-3-phenyl-5-piperidino-                                                                   500    3-Slight                                       pyrazolium iodide                                                             ______________________________________                                    

From these data it is apparent that 1,2-dimethyl-3-(2,3 or4-methylpiperidino)-5-phenylpyrazolium salts are preferred fungicidalagents effective for the control of powdery mildew on wheat.

The following examples illustrate the preparation of the compoundsemployed as fungicides herein.

EXAMPLE 3 Preparation of 1-methyl-3-phenyl-2-pyrazolin-5-one

Ethyl benzoylacetate (1,538 g, 8 moles) dissolved in isopropanol (6 l )is placed in a 12 l flask under an atmosphere of nitrogen.Methylhydrazine (410 g, 8.7 moles, 98%) in isopropanol (800 ml) is addedwith stirring in a dropwise manner to the ethyl benzoylacetate solutionprewarmed to about 80°C. During the addition the external heating isremoved. Seeding of the reaction mixture with the product at the pointof one-third addition of methylhydrazine causes a copious precipitate ofproduct. This procedure eliminates a large exotherm from occurring at alater stage. After the addition is complete, the reaction mixture isheld at about 80°C. for 2 hours. Cooling the slurry to 20°C. andfiltering off the solid, a yield of 1,131 g (81%) of product afterdrying with a melting point equal to 211° C. is obtained.

EXAMPLE 4 Preparation of 5-chloro-1-methyl-3phenylpyrazole

To a solution of phosphorous oxychloride (2,015 g, 19 moles) is addedsolid 1-methyl-3-phenylpyrazolin-5-one (2,073 g, 11.9 moles) withstirring and warming. At 100°C. the mixture becomes homogeneous. Thereflux temperature rises from 119°C. to 143°C. over a period of 30hours. After cooling the mixture is poured into ice and water (8 l) withstirring. After 4 hours the slurry is filtered and the filter cake addedto 4 l of water containing 1.5 l of 10% sodium hydroxide solution withstirring. Removal of the solid by filtration followed by arecrystallization from hexane yields 1,523 g of product, having amelting point ranging from 61°C. to 62°C.

EXAMPLE 5 Preparation of 3-chloro-1,2-dimethyl-5-phenylpyrazolium methylsulfate, utilizing one of two methods METHOD (A)

Dimethyl sulfate (30 g, 0.22 mole) is added to a stirred solution of5-chloro-1-methyl-5-phenylpyrazole (39.5 g, 0.2 mole) in dry xylene (350ml) and the reaction mixture is warmed to 105°C. to 115°C. for 18 hours.A brown syrup separates out, the reaction is cooled and the xylene isdecanted off. Dry acetone (300 ml) is added and after stirring a whiteprecipitate separates out and is filtered off, mp 100°C. to 102°C. 33.8g, (55%). Recrystallization from dry acetone-toluene (1:1) gives whiteneedles mp 102°C. to 104°C.

Analysis calculated for C₁₂ H₁₅ N₂ ClSO₄ : C, 45.22; H, 4.74; N, 8.79;Cl, 11.13. Found: C, 45.31; H, 4.81; N, 8.93; Cl, 11.24.

METHOD (B)

To a solution of dimethyl sulfate (1,596 g, 12.66 moles) at 70°C. to74°C. is added 5-chloro-1-methyl-3-phenylpyrazole (1,523 g, 7.912moles). During the exothermic addition the heat source is removed. Afterthe exothermic reaction has ceased the reaction mixture is maintained at80°C. by external heating for 2 hours and then is poured into toluene.Toluene is decanted off, leaving a residual syrup, which is treated withadditional toluene and decanted off as above. The syrup is dissolved inchloroform, filtered, and the filtrate evaporated to an oil, whichcrystallizes from acetone to yield 1.52 kg, (60.3%) mp 95°C. to 96°C.

EXAMPLE 6 Preparation of 3-chloro-1,2-dimethyl-5-phenylpyrazolium iodide

To an aqueous solution of 1,2-dimethyl-3-chloro-5-phenylpyrazoliummethyl sulfate is added a saturated aqueous solution of sodium iodide at5°C. A copious precipitate is formed and filtered off. The solid isdissolved in methylene chloride and precipitated with diethyl ether toyield almost white crystals mp 162°C. to 164°C.

Analysis calculated for C₁₁ H₁₂ N₂ Cll: C, 39.49; H, 3.62; N, 8.38; Cl,10.64; I, 37.93. Found: C, 39.46; H, 3.61; N, 8.44; Cl, 10.47; I, 37.85.

EXAMPLE 7 Preparation of 3-cyclohexyl-1-methyl-2-pyrazolin-5-one

To ethyl 3-oxo-cyclohexanepropionic acid (4.4 g, 0.234 mole) inn-propanol (500 ml) is added dropwise with stirring under nitrogen at80°C. methylhydrazine (13.8 g, 0.3 mole). After heating at reflux during5 hours, the reaction is cooled and evaporated to a residual oil.Crystallization from ethylacetate gives a white powder mp 170.5°C. to172°C.

Analysis calculated for C₁₀ H₁₀ N₂₀ ; C, 66.63 H, 8.95; N, 15.54. Found:C, 66.59; H, 9.07; N, 15.69.

EXAMPLE 8 Preparation of 5-chloro-3-cyclohexyl-1-methylpyrazole

Phosphorus oxychloride (15.3 g, 0.1 mole) is added to3-cyclohexyl-1-methyl-2-pyrazolin-5-one and the mixture stirred andheated at 120°C. to 135°C. for 8 hours. The cooled reaction mixture isthen poured into ice-water, made alkaline with 1% aqueous sodiumhydroxide and extracted with methylene chloride. Removal of solventunder reduced pressure, then in vacuo at 70°C. affords an oil, 8 g,(93.8%).

Analysis calculated for C₁₀ H₁₅ N₂ Cl; C, 60.45; H, 7.61; N, 14.10; Cl,17.85. Found: C, 60.28; H, 7.55; N, 14.20; Cl, 17.79.

EXAMPLE 9 Preparation of 3-chloro-5-cyclohexyl-1,2-dimethylpyrazoliummethyl sulfate [and hydrogen sulfate (1:1)]

A mixture of 5-chloro-3-cyclohexyl-1-methylpyrazole (7 g, .0352 mole)and dimethyl sulfate (8.82 g, 0.07 mole) is heated to 80°C. and theheating source then removed. The reaction temperature rises to 88°C. andthen, after the exotherm, the temperature is maintained at 80°C. byexternal heating for 6 hours. Toluene (100 ml) is added to the cooledreaction and the mixture is set aside overnight at room temperature andthen a waxy solid is filtered off. Crystallization from methylenechloride-ether affords a granular product, mp 70°C. to 73.5°C., 11.2 g(100%). NMR and infrared spectra indicate a mixture of CH₃ SO₄ and HSO₄anions.

Analysis calculated for C₁₂ H₂₁ N₂ ClSO₄ (as CH₃ SO₄): C,44.36; H, 6.57;N, 8.63; S, 9.87; Cl, 10.92. Found C, 41.34; H, 6.24; N, 8.14; S, 9.12;Cl, 10.31.

A portion of the above compound is readily converted to the perchloratewhose melting point ranges from 216°C. to 218°C.

EXAMPLE 10 Preparation of 3,4,5-Tribromo-1-methylpyrazole

To 3,4,5-tribromopyrazole (4.5 g, 0.15 mole) in 3N aqueous sodiumhydroxide (6 g, 0.15 mole) is added at room temperature with stirringdimethyl sulfate (19 g, 0.15 mole). After 10 minutes a solid separatesout. An additional gram of dimethyl sulfate is added and the mixture isstirred for 3 days, filtered and the precipitate water washed and airdried to yield 33 g (73%), mp 85°C. to 86°C. Crystallization fromcyclohexane yields desired solid product whose melting point ranges fromabout 90°C. to 91°C.

Analysis calculated for C₄ H₃ N₂ Br₃ : C, 15.07; H, 0.95; N, 8.79; Br,75.21. Found: C, 15.16; H, 0.82; N, 8.7; Br, 75.36.

EXAMPLE 11 Preparation of 3,4,5-tribromo-1,2-dimethylpyrazolium methylsulfate (and perchlorate)

A stirred suspension of 1-methyl-3,4,5-tribromopyrazole (19.3 g, 0.06mole) in dimethyl sulfate (80 ml) is stirred and heated at 130°C. to135°C. for 6 hours. On cooling and setting aside overnight, a solid isobtained and filtered off, benzene washed and air dried to yield 18.7 g,(70%) whose melting point ranges from 199°C. to 203°C.

Analysis calculated for C₆ H₉ N₂ Br₃ SO₄ : C, 16.19; H, 2.04; N, 6.29;Br, 53.88; S, 7.20. Found: C, 16.19; H, 1.99; N, 6.38; Br, 53.98; S,7.31.

Treatment of the above methyl sulfate compound with aqueous perchloricacid affords the perchlorate whose melting point ranges from 300°C. to300.5°C.

EXAMPLE 12 Preparation of 1,2-dimethyl-3-phenyl-5-piperidinopyrazoliumiodide and perchlorate

Piperidine (2.56 g, 0.03 mole) is added to1,2-dimethyl-3-chloro-5-phenylpyrazolium methyl sulfate (4.77 g, 0.015mole) in absolute ethanol (30 ml) and the mixture stirred with a barmagnet and heated under reflux for 4 hours. After cooling, the reactionmixture is evaporated under reduced pressure to a brown oil, and thendissolved in 50 ml of aqueous saturated sodium bicarbonate solution. Theaqueous layer is extracted with ether and this organic layer discarded,then with chloroform (3×100 ml). Evaporation of the chloroform layeraffords 1,2-dimethyl-3-phenyl-5-piperidinopyrazolium methyl sulfate as aviscous oil. The oil is redissolved in water and saturated aqueouspotassium iodide solution is added. (Sodium iodide is also equallyeffective). An immediate copious white precipitate of1,2-dimethyl-3-phenyl-5-piperidinopyrazolium iodide is formed, thenfiltered and washed with ice cold water to give 3.37 g, (56%) of productmp 179°C to 180°C. The melting point is unchanged by dissolving inchloroform, filtering and reprecipitating with diethyl ether andfiltering off the solid. For analysis see Table I, compound 1.

Treatment of a portion of the iodide dissolved in warm water with 10%aqueous perchloric acid gives a white solid which after cooling to 10°Cis filtered off, mp 137°C to 138°C; see compound 2, Table I. Thismaterial is also obtained directly by treating an aqueous solution ofthe methyl sulfate (above) with 10% sodium perchlorate and filtering offthe product.

EXAMPLE 13 Preparation of 1,2-Dimethyl-3,5-dipiperidinopyrazoliumbromide

4-Bromo-1,2-dimethyl-3,5-dipiperidinopyrazolium bromide (6.3 g, 0.015mole) is dissolved in methanol (150 ml) and sodium hydroxide (1.2 g, 0.3mole) and treated with 10% palladium on carbon. The mixture ishydrogenated at 25°C and absorbs hydrogen (290 ml) uncorrected (86%) in25 minutes. The catalyst is filtered off, washed with ethanol andaqueous hydrogen bromide (10 ml) is added. The mixture is evaporated invacuo to an oil, which is dissolved in chloroform and precipitated withdiethyl ether to give a white powder on filtration mp 211°C. to 212°C,3.4 g, (69%). Analysis see compound 10, Table IV.

A small amount of the bromide is dissolved in water and converted with10% perchloric acid in quantitative yield to the perchlorate mp 171°C to172°C, compound 11, Table IV.

EXAMPLE 14

Following the procedure of Method A or Method B above, there areobtained the compounds identified in Table IV in good yields and purity.

                                      Table IV                                    __________________________________________________________________________                  Preparation of                                                  No.                                                                              N(CH.sub.2).sub.n                                                                      X     R.sub.4                                                                         R.sub.5                                                                             Method    (%) Yield                                                                           (°C) mp                                                                       Analysis                     |                                       Calculated                                                                           % Found               R.sub.3                                                                       __________________________________________________________________________     1          I.sup.-                                                                             H       A         56    179-180                                                                              C 30.14                                                                              C 49.74                                         A salt(NaI on          H 5.80 H 5.61                                          intermediate           N 10.96                                                                              N 10.91                                         (CH.sub. 3 SO.sub.4)                                 2          ClO.sub.4 .sup.-                                                                    H       A         95    137-138                                                                              C 54.01                                                                              C 53.80                                         A acid(HClO.sub.4 on   H 6.23 H 6.07                                          intermediate           N 11.80                                                                              N 11.71                                         (CH.sub.3 SO.sub.4)                                  3          CH.sub.3 SO.sub.4 .sup.-                                                            H       A         63    112-114                                                                              C 55.57                                                                              C 55.14                                                                H 6.86 H 6.70                                                                 N 11.44                                                                              N 12.17                4          I.sup.-                                                                             H       A         75    122-124.5                                                                            C 51.40                                                                              C 51.39                                                                H 6.09 H 6.23                                                                 N 10.58                                                                              N 10.38                5          I.sup.-                                                                             H       A         45    184.5-185                                                                            C 51.40                                                                              C 51.30                                                                H 6.09 H 6.07                                                                 N 10.58                                                                              N 10.55                6          I.sup.-                                                                             H       A         51    151-152                                                                              C 51.40                                                                              C 51.07                                                                H 6.09 H 6.13                                                                 N 10.56                                                                              N 10.74                7          I.sup.-                                                                             H       A         51    143-144.5                                                                            C 51.40                                                                              C 50.38                                                                H 6.09 H 6.08                                                                 N 10.58                                                                              N 10.54                8          Br.sup.-                                                                            Br      B         88    170-170.5                                                                            C 42.67                                                                              C 42.77                                                                H 6.21 H 45.98                                                                N 13.27                                                                              N 13.28                                                                Br                                                                              37.85                                                                              Br                                                                              37.93                9          ClO.sub.4 .sup.-                                                                    Br      B         --    154-155                                                                              C 40.77                                                                              C 40.79                                         Acid(HClO.sub.4 on     H 5.93 H 6.01                                          Br.sup.-)              N 12.68                                                                              N 12.77                                                                Br                                                                              18.09                                                                              Br                                                                              18.14               10          Br.sup.-                                                                            H       B         69    211-212                                                                              C 52.48                                                                              C 52.33                                         Hydrogenration         H 7.93 H 7.66                                          Pd/C/H.sub.2 /NaOH     N 16.32                                                                              N 16.04                                         on Compound 9          Br                                                                              23.28                                                                              Br                                                                              22.64               11          ClO.sub.4 .sup.-                                                                    H       B         95    170-171                                                                              C 49.64                                                                              C 49.38                                         HClO.sub.4 on          H 7.50 H 7.68                                          compound 10            N 15.44                                                                              N 15.08               12          ClO.sub.4 .sup.-                                                                    H       A         54    110-112                                                                              C 55.21                                                                              C 54.01                                         Acid(HClO.sub.4 on     H 6.54 H 6.51                                          compound 14 the        N 11.36                                                                              N 10.92                                         CH.sub.3 SO.sub.4 .sup.-)                           13          Br.sup.-                                                                            H       A         60    144-146                                                                              C 58.28                                                                              C 57.92                                         Acid(HBr on            H 6.91 H 6.77                                          compound 14 the        N 11.99                                                                              N 11.89                                         CH.sub.3 SO.sub.4 .sup.-)                           14          CH.sub.3 SO.sub.4 .sup.-                                                            H       A         67    glass  C 56.68                                                                              C 56.39                                                                H 7.14 H 7.15                                                                 N 11.02                                                                              N 11.20               15          Cl.sup.-.2H.sub.2 O                                                                 H       Ion exchange on                                                                         13    70.5-72                                                                              C 59.90                                                                              C 60.64                                         Dowex 1-X8-Cl                                                                           47           H 8.66 H 8.11                                          anion, using           N 11.67                                                                              N 12.58                                         compound 14,           Cl                                                                              11.61                                                                              Cl                                                                              10.21                                         CH.sub.3 SO.sub.4 .sup.-                            16          CH.sub.3 SO.sub.4 .sup.-                                                            H       A         67    glass  C 56.68                                                                              C 55.07                                                                H 7.14 H 7.09                                                                 N 11.02                                                                              N 10.60               17          Cl.sup.-                                                                            H       Ion exchange on                                                                         60    oil    N 12.27                                                                              N 11.70                                         Dowex 1-X8-Cl          Cl                                                                              20.72                                                                              Cl                                                                              19.92                                         anion using                                                                   compound 16                                         18          ClO.sub.4 .sup.-                                                                    H       A         --    94-95  C 55.21                                                                              C 54.94                                         Salt NaClO.sub.4 on    H 6.54 H 6.48                                          compound 16            N 11.36                                                                              N 11.38               19          CH.sub.3 SO.sub.4 .sup.-                                                            H       A         98    glass  C*                                                                              55.78                                                                              C 51.91                           Cl.sup.- (75:25)                     H*                                                                              8.58 H 8.16                                                                 N*                                                                              10.84                                                                              N 10.38                                                                S*                                                                              8.27 S 6.83                                                                 Cl                                                                              --   Cl                                                                              2.56                20          I.sup.-                                                                             H       A         --    glass  C 50.62                                                                              C 50.59                                         Salt.NaI on            H 7.50 H 7.89                                          compound 19            N 10.42                                                                              N 10.42                                                                I 31.47                                                                              I 30.60               21          I.sup.-                                                                             H       A         --    99-100 C 49.39                                                                              C 47.99                                         Salt.NaI on            H 7.25 H 7.24                                          CH.sub.3 SO.sub.4 .sup.- salt                                                                        N 10.80                                                                              N 10.42                                                                I 32.60                                                                              I 31.61               22          I.sup.-                                                                             Br      A         75    193-194                                                                              C 42.87                                                                              C 42.81                                                                H 4.87 H 4.33                                                                 N 8.82 N 8.82                                                                 Br                                                                              16.78                                                                              Br                                                                              16.90                                                                I 26.65                                                                              I 26.68               23          I.sup.-                                                                             Br      A         63    211-213                                                                              C 42.87                                                                              C 42.58                                                                H 4.87 H 5.00                                                                 N 8.82 N 8.78                                                                 Br                                                                              16.78                                                                              Br                                                                              16.89                                                                I 26.65                                                                              I 26.56               24          ClO.sub.4 .sup.-                                                                    Br      A          6    197-199                                                                              N 9.20 N 8.91                25          I.sup.-                                                                             Br      A         16    201-202                                                                              C 41.58                                                                              C 39.15                                                                H 4.58 H 4.38                                                                 N 9.09 N 8.66                                                                 Br                                                                              17.29                                                                              Br                                                                              16.30               __________________________________________________________________________     *[as CH.sub.3 SO.sub.4                                                   

I claim:
 1. A method for protecting plants from attack by fungicomprising: applying to said plants a fungicidally effective amount of acompound having a formula selected from the group consisting of:##SPC7##wherein R₃ represents a member selected from the groupconsisting of hydrogen, methyl, hydroxy and phenyl; R₄ represents amember selected from the group consisting of hydrogen, and halogen; R₅represents a member selected from the group consisting of phenyl,cyclohexyl and ##EQU3## X represents an anion with a charge of 1 or 2; nis five; m represents an integer selected from 1 and 2; and HB is anacid of sufficient strength to form a stable salt with the ##EQU4##group.
 2. The method according to claim 1 wherein said compound is aformula (I) pyrazolium salt and the plants to be protected are cerealgrain plants.
 3. The method according to claim 1 wherein the fungusorganism is powdery mildew and the compound is applied in liquid form asa spray containing 100 ppm to 5600 ppm of the formula (I) pyrazoliumsalt compound.
 4. The method according to claim 1 wherein said compoundis: 1,2-dimethyl-3-phenyl-5-piperidinopyrazolium iodide, hydroiodide. 5.The method according to claim 1 wherein the compound is:1,2-dimethyl-3-phenyl-5-piperidinopyrazolium perchlorate, perchloricacid salt.
 6. The method according to claim 1 wherein the compound is:1,2-dimethyl-3-(4-methylpiperidino)-5-phenylpyrazolium iodide.
 7. Themethod according to claim 1 wherein the compound is:4-bromo-1,2-dimethyl-3,5-dipiperidinopyrazolium bromide, hydrobromide.8. The method according to claim 1 wherein the compound is:1,2-dimethyl-3,5-dipiperidinopyrazolium perchlorate.
 9. The methodaccording to claim 1 wherein the compound is:1,2-dimethyl-3-(3-methylpiperidino)-5-phenylpyrazolium perchlorate. 10.A method for controlling fungi by contacting said fungi with afungicidally effect amount of a compound according to claim 1 having aformula selected from the group consisting of: ##SPC8##wherein R₃represents a member selected from the group consisting of hydrogen,methyl, hydroxy and phenyl; R₄ represents a member selected from thegroup consisting of hydrogen, and halogen; R₅ represents a memberselected from the group consisting of phenyl, cyclohexyl and ##EQU5## Xrepresents an anion with a charge of 1 or 2; n is five; m represents aninteger selected from 1 and 2; and HB is an acid of sufficient strengthto form a stable salt with the ##EQU6## group.
 11. A method according toclaim 10 wherein the fungus organism is powdery mildew and the compoundis applied in liquid form as a spray containing 100 ppm to 5600 ppm ofthe formula (I) pyrazolium salt compound.